Is more better? A comparison of tri- and tetrapeptidic catalysts

From an enzymatic perspective, there is a general notion that the bigger and more complex a catalytically active peptide is the more enzyme-like and the better it should become. But is this really true? We have tackled this question firstly by screening split-and-mix-libraries of tri- and tetrapeptides for members that catalyze aldol reactions. Then, the catalytic performance of all possible diastereoisomers of related tri- and tetrapeptidic catalysts of the type H-Pro-Pro-Glu/Asp-NH₂ and H-Pro-Pro-Glu/Asp-Pro-NH₂ in aldol and conjugate addition reactions was compared.